The primary focus of my research program is to understand how the autonomic nervous system regulates the human cardiovascular system. The overall goal of this grant application is to enhance understanding of how the peripheral and central chemoreflexes modify arterial baroreflex function in humans, focusing on muscle sympathetic nerve activity and heart rate. Chemoreflexes and baroreflexes play a major role in control of the cardiovascular system via the profound influences they exert on autonomic outflow. However, the interaction of these powerful reflex systems is not completely understood in humans. In this Context, the specific aims for this grant application are designed to address the following questions: 1) Does isocapnic hyperpnea alter arterial baroreflex function in humans? 2a) Does isocapnic hypoxia alter arterial baroreflex function in humans? 2b) Does the selective peripheral chemoreceptor stimulant almitrine mimic the effects of hypoxia on arterial baroreflex function in humans? 3) Does hyperoxic hypocapnia alter arterial baroreflex function in humans? Throughout this application, we exploit state-of-the-art methods and propose highly controlled studies in conscious human volunteers, probing questions raised by animal studies in this area. These studies will advance our understanding of basic cardiovascular regulation in humans and how it is modified by changes in chemoreflex stimulation. Further, these studies will provide a foundation of basic understanding that will be necessary to explain related pathophysiologies such as heart failure, COPD, and sleep apnea. By addressing these aims, we will extend insights that are now only available in animals to a poorly understood area of cardiovascular regulation in humans.